These compounds surprisingly evidence a selective affinity to 5HT-6 receptors. They are accordingly suitable for use in the treatment and prevention of central nervous disorders such as, for example, psychoses, schizophrenia, manic depressions (Bryan L. Roth et al., J. Pharmacol. Exp. Ther., 268, pages 1403-1410 (1994)), depressions (David R. Sibley et al., Mol. Pharmacol., 43, pages 320-327 (1993)), neurological disorders (Anne Bourson et al., J. Pharmacol. Exp. Ther., 274, pages 173-180 (1995); R. P. Ward et al., Neuroscience, 64, pages 1105-1110 (1995)), memory disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's chorea (Andrew J. Sleight et al., Neurotransmissons, 11, pages 1-5 (1995)).
Preferred is the treatment of Alzheimer's disease.
Objects of the present invention are the novel compounds of formula I-A and I-B and their pharmaceutically useable salts, the use of these compounds as therapeutically active substances, the manufacture of these compounds, medicaments containing one or more of these compounds, optionally in the form of one of their pharmaceutically useable salts, as well as the production of such medicaments.
Preferred compounds of general formula I-A are those in which R.sup.3 represents amino, such as, for example
3-benzenesulphonyl-5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-yl amine,
3-(4-isopropyl-benzenesulphonyl) -5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]-pyrimidin-7-ylamine,
5-methyl-2-methylsulphanyl-3-(naphthalene-2-sulphonyl) -pyrazolo[1,5-a]pyrimidin-7-ylamine,
3-(4-fluoro-benzenesulphonyl)-5-methyl-2-methylsulphanyl-pyrazolo[1,5-a]pyr imidin-7-ylamine,
3-benzenesulphonyl-5-cyclopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin -7-ylamine,
3-benzenesulphonyl-2-methylsulphanyl-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1 ,5-a]pyrimidin-8-ylamine,
3-benzenesulphonyl-5-isopropyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7 -ylamine,
5-methyl-2-methylsulphanyl-3-(toluene-2-sulphonyl)-pyrazolo[1,5-a]pyrimidin -7-ylamine,
5-methyl-2-methylsulphanyl-3-(toluene-3-sulphonyl)-pyrazolo[1,5-a]pyrimidin -7-ylamine,
3-benzenesulphonyl-5-methoxymethyl-2-methylsulphanyl-pyrazolo[1,5 -a]pyrimidin-6-ylamine,
3-benzenesulphonyl-N5,N5-dimethyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidi n-5,7-diamine,
3-benzenesulphonyl-N5-(2-dimethylamino-ethyl)-2-methylsulphanyl-pyrazolo[1, 5-a]pyrimidin-5,7-diamine,
3-benzenesulphonyl-5-(4-methyl-piperazin-1-yl)-2-methylsulphanyl-pyrazolo[1 ,5-a]pyrimidin-7-ylamine and
3-benzenesulphonyl-5-dimethylamineomethyl-2-methylsulphanyl-pyrazolo[1,5-a] pyrimidin-7-ylamine.
Additionally preferred, compounds of formula I-A are those in which R.sup.3 represents piperazinyl, such as, for example,
3-benzenesulphonyl-5-methyl-2-methylsulphanyl-7-piperazin-1-yl-pyrazolo[1,5 -a]pyrimidine,
3-(4-tert-butyl-benzenesulphonyl)-5-methyl-2-methylsulphanyl-7-piperazin-1- yl-pyrazolo[1,5-a]pyrimidine,
3-benzenesulphonyl-5,6-dimethyl-2-methylsulphanyl-7-piperazin-1-yl-pyrazolo -[1,5-a]pyrimidine,
3-benzenesulphonyl-2-methylsulphanyl-7-piperazin-1-yl-5-propyl-pyrazolo[1,5 -a]pyrimidine,
3-benzenesulphonyl-5-cyclopropyl-2-methylsulphanyl-7-piperazin-1-yl-pyrazol o[1,5-a]pyrimidine,
3-benzenesulphonyl-2-methylsulphanyl-8piperazin-1-yl-6,7-dihydro-5H-cyclo-p enta[d]pyrazolo[1,5-a]pyrimidine,
3-benzenesulphonyl-2-methylsulphanyl-8-piperazin-1-yl-5H,7H-pyrazolo[1,5-a] thieno[3,4-d]pyrimidine,
5-methyl-2-methylsulphanyl-7-piperazin-1-yl-3-(thiophen-2-sulphonyl)-pyrazo lo[1,5-a]pyrimidine,
3-benzenesulphonyl-2-ethyl-8-piperazin-1-yl-6,7-dihydro-5H-cyclopenta[d]pyr azolo[1,5-a]pyrimidine and
5-methyl-2-methylsulphanyl-7-piperazin-1-yl-3-(toluol-2-sulphonyl)-pyrazolo [1,5-a]pyrimidine.
Furthermore, there are preferred compounds of formula I-A and I-B in which R.sup.3 represents methylpiperazinyl, such as, for example,
3-benzenesulphonyl-5-cyclopropyl-2-methylsulphanyl-7-(4-methylpiperazin-1-y l) -pyrazolo[1,5-a]pyrimidine,
3-benzenesulphonyl-8-(4-methyl-piperazin-1-yl)-2-methylsulphanyl-6,7-dihydr o-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine,
3-benzenesulphonyl-8-(4-methyl-piperazin-1-yl)-2-methylsulphanyl-5H,7H-pyra zolo[1,5-a]thieno[3,4-d]pyrimidine,
3-benzenesulphonyl-5-isopropyl-7-(4-methyl-piperazin-1-yl)-2-methylsulphany l-pyrazolo[1,5-a]pyrimidine and
2-[3-benzenesulphonyl-7-(4-methyl-piperazin-1-yl)-2-methylsulphanyl-pyrazol o-[1,5-a]pyrimidine-5-yloxy]-ethanol.
8-Benzenesulphonyl-7-methylsulphanyl-pyrazolo[1,5-a][1,3,5]triazin-4-ylamin e and 8-benzenesulphonyl-2-methyl-4-(4-methylpiperazin-1-yl)-7-methylsulphanyl-p yrazolo[1,5-a][1,3,5]triazine are other preferred triazines of general formula I-B.
The term "lower alkyl" as used in the present description denotes residues from 1 to 7, preferably from 1 to 4, carbon atoms, such as, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl and t-butyl.
The term "lower alkoxy" denotes a lower alkyl residue in the sense of the foregoing definition bonded via an oxygen atom, such as, for example, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy and t-butoxy.
The term "lower alkylamino" denotes a lower alkyl residue in the sense of the foregoing definition bonded via an NH group, such as, for example, methylamino and ethylamino.
The term "di-lower-alkylamino" represents identical or different lower alkyl residues in the sense of the foregoing definition bonded via a nitrogen atom, such as, for example, dimethylamino, diethylamino or methyl-ethyl-amino.
The term "halogen" includes fluorine, chlorine, bromine and iodine.
The term "lower thioalkyl" denotes a lower alkyl residue in the sense of the foregoing bonded via a sulphur atom.
The preparation of the novel compounds can be effected in a manner known to one skilled in the art. Specifically, compounds of formula I-A may be synthesized as is described in Examples 1-123. Compounds of formula I-B maybe synthesized as is described in Examples 124-129. Furthermore, Schemes 1-3 provide a general overview with respect to the alternatives available for the preparation of these novel compounds, the starting compounds of formula III in Scheme 1 being prepared in a manner analogous to described methods.
The compounds of formula I-A and I-B also include those compounds in which hydrogen can be replaced by tritium.